This invention relates to the production of vaccines against bovine parainfluenza virus type 3 (PI-3), which is classified as a paramyxovirus. More specifically, synthetic DNA genes coding for PI-3 proteins may be produced as disclosed herein. These genes may be used for the production of the selected viral protein by transformed cells, the biosynthetic protein being useful in a vaccine, diagnostic kit or the like. The synthetic gene itself will be useful as a diagnostic agent.
Bovine parainfluenza virus type III, also called PI-3 or shipping fever virus, has considerable pathologic and economic impact as a principal factor in the initiation of an acute respiratory disease syndrome in cattle. Shipping fever syndrome can be initiated by PI-3 viral infection, usually under stressful conditions such as those associated with the shipping or feedlot management of cattle. The viral infection is believed to predispose the animals to bacterial infection, for example by Pasteurella multocida or Pasteurella haemolytica, which results in shipping fever syndrome. Annual economic losses due to diminished body weight, expensive treatments and delayed marketability are estimated in excess of $75 million. A similar virus infects sheep, leading to a respiratory disease very similar to shipping fever syndrome.
Viral vaccines, including live attenuated vaccines, have been employed for about 20 years with some success. For example, live bacterial vaccines produced from chemically modified strains of Pasteurella multocida and Pasteurella haemolytica are disclosed in U.S. Pat. No. 4,293,545 (Kucera).
The success of the viral vaccine approach for the prevention of parainfluenza viruses has been restricted by the limited effectiveness of current vaccines. This is due, in part, to interference from existing antibodies or inhibition by other viral vaccines. In addition, use of live viral vaccines on breeding animals may result in fetal infection and subsequent abortion.
Recently, it has become possible to produce a synthetic gene by formulating a bimolecular double-stranded DNA copy of a messenger RNA (mRNA) molecule. The synthetic gene produced in this manner will code for that protein which was the translation product of the selected mRNA. An example of this genetic engineering process is disclosed in U.S. Pat. No. 4,357,421 (Emtage et al.) where it is used to produce a synthetic gene for an influenza haemagglutinin protein. Influenza viruses contain no DNA; rather, they contain a segmented negative strand viral RNA (vRNA) genome which is replicated during infection to produce viral messenger RNA (mRNA) and templates for the production of further vRNA. Influenza virus genomes are of the segmented type, that is, each gene is present as a separate piece of vRNA which is transcribed separately to produce mRNAs. The process disclosed by Emtage et al. utilizes isolated vRNA as a direct template for the synthetic gene of interest.